GVHD: Fighting the good fight

Understanding the most dangerous complication of bone marrow transplants

If your immune system were completely replaced with the immune system from someone else, you might expect your body to react, right?

And if this “regime change” of the immune system took place shortly after your body went through intensive chemo, you might expect it to react pretty violently.

What we’re talking about here is one of the most common and serious side effects that bone marrow transplant patients face: graft-versus-host disease (GVHD). In simple terms, GVHD happens when a child’s new immune system from the transplant (the graft) recognizes the child’s own cells (the host) as the enemy and attacks them.

A little goes a long way

More than half of the children diagnosed with cancer who receive bone marrow transplants develop GVHD, which is lethal when it can’t be controlled. But a little GVHD is not always a bad thing. The donor immune cells attack not only the normal cells of your body, but also any remaining cancer cells that had weren’t killed by the chemotherapy. In fact, patients who experience mild GVHD have a lower risk of relapse than patients who do not develop any GVHD at all.

Too much of a good thing

Severe GVHD is bad, however, and can be fatal – especially when it targets the gastrointestinal (GI) tract. The treatment for GVHD is immunosuppressant medications that knock the wind out of the immune system. But it’s often like walking a tightrope – we have to be careful with drugs that further weaken a newly transplanted immune system, because they increase the risk for serious and life-threatening infections.

So far we’ve been talking about acute GVHD, which occurs shortly after the transplant, usually within 3 months. There is also a second kind of GVHD, called chronic GVHD, which occurs later after transplant. Chronic GVHD is also difficult to treat, and some patients can become very ill when organs such as the lungs are affected.

U-M scientists have identified a key biomarker of GVHD of the GI tract, shown here in brown in this image of the intestine.

Changing the face of GVHD

Here at U-M, we have several teams of doctors and scientists working to make bone marrow transplants safer and more effective for children.

Improving how we care for kids today

U-M offers a specialized clinic for bone marrow transplant patients with chronic GVHD to help them cope with the effects of their disease. Our goal is to restore normalcy for children with chronic GVHD so they can go back to school and live normal lives again.

The clinic offers patients a comprehensive evaluation, discussion of potential treatment options and access to clinical trials with cutting-edge therapies. Because GVHD can target just about any area of the body, specialists from almost all fields of medicine evaluate patients and offer a plan of coordinated care.

Improving what we know for kids tomorrow

Our goal is to offer personalized care, using the right treatment in the right amount at the right time, which is essential when it comes to GVHD. Doctors have long struggled to individualize therapy for each patient, but there has been no new therapy for GVHD in more than 40 years.

For the past ten years we have led a research team to devise a blood test that can diagnose GVHD, that can determine who will respond to treatment, and that could even identify which patients will get GVHD before any symptoms appear. We have recently discovered several such tests (called biomarkers), and right now we are analyzing samples taken from children receiving bone marrow transplants all across the country to determine which tests are best. We are also analyzing samples from patients around the world, and training doctors from other countries on how to perform these tests. Our scientists are also using these tests to better understand the biology of GVHD and are already trying completely new approaches to prevent and treat GVHD in preclinical studies.

The advances we’ve made in treating GVHD even in just the last few months are breathtaking. With so much on the line, and so much potential to make things better for kids, we’ve redoubled our efforts to translate this new knowledge into the care we deliver every day in our beautiful new C.S. Mott Children’s hospital.

James Ferrara, MD, DSc, is a pediatric oncologist at C.S. Mott Children’s Hospital. Prior to joining the U-M team, he completed his residency in pediatrics at Boston Children’s Hospital and his fellowship in pediatric hematology/oncology at Boston Children’s/Dana-Farber Cancer Institute. He then joined the faculty of Harvard Medical School where he remained until he came to the University of Michigan in 1998. His principal focus is the pathophysiology of graft versus host disease (GVHD).

John Levine, MD, is a pediatric oncologist and the Clinical Director of the Pediatric Blood and Marrow Transplantation Program at C.S. Mott Children’s Hospital. Dr. Levine completed his residency in pediatrics at Children’s Hospital of Los Angeles, followed by a pediatric hematology/oncology fellowship at Memorial Sloan-Kettering Cancer Center in New York City. He has been a member of the University of Michigan faculty since 1995.

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University of Michigan C.S. Mott Children’s Hospital is consistently ranked one of the best hospitals in the country. It was nationally ranked in all ten pediatric specialties in U.S. News Media Group’s “America’s Best Children’s Hospitals,” and among the 10 best children’s hospitals in the nation by Parents Magazine. In December 2011, the hospital opened our new 12-story, state-of-the-art facility offering cutting-edge specialty services for newborns, children and women.

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